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Chlordane-Induced Neurotoxicosis in Urban and Suburban Detroit, Michigan Striped Skunks (Mephitis mephitis)
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Biodegradation of Naphthenic Acids in the Presence of Spirulina platensis Algae
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Health Risk for Non-Dietary Children’s Exposure to Heavy Metals in Postindustrial Areas in Upper Silesia, Poland
Journal Description
Toxics
Toxics
is an international, peer-reviewed, open access journal on all aspects of the toxic chemicals and materials, published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, AGRIS, and other databases.
- Journal Rank: JCR - Q1 (Toxicology) / CiteScore - Q1 (Chemical Health and Safety)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 18.1 days after submission; acceptance to publication is undertaken in 1.9 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
4.1 (2024);
5-Year Impact Factor:
4.6 (2024)
Latest Articles
The Crime of Vehicular Homicide in Italy: Trends in Alcohol and Drug Use in Fatal Road Accidents in Lazio Region from 2018 to 2024
Toxics 2025, 13(7), 607; https://doi.org/10.3390/toxics13070607 (registering DOI) - 19 Jul 2025
Abstract
In Italy, the law on road homicide (Law no. 41/2016) introduced specific provisions for drivers who cause severe injuries or death to a person due to the violation of the Highway Code. The use of alcohol or drugs while driving constitutes an aggravating
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In Italy, the law on road homicide (Law no. 41/2016) introduced specific provisions for drivers who cause severe injuries or death to a person due to the violation of the Highway Code. The use of alcohol or drugs while driving constitutes an aggravating circumstance of the offence and provides for a tightening of penalties. Our study aims to report on the analysis performed on blood samples collected between January 2018 and December 2024 from drivers convicted of road homicide and who tested positive for alcohol and/or drugs. The majority of the involved subjects were males belonging to the 18–30 and 41–50 age groups. Alcohol, cocaine and cannabinoids were the most detected substances and the most frequent polydrug combination was alcohol and cocaine. We also investigated other influencing factors in road traffic accidents as the day of the week and the time of the day in which fatal road traffic accident occurred, and the time elapsed between the road accident and the collection of biological samples. Our data, in line with the international scenario, strongly support that, in addition to the tightening of penalties, raising awareness plays a key role in preventing alcohol- and drug-related traffic accidents by increasing risk perception and encouraging safer driving behaviors.
Full article
(This article belongs to the Special Issue Current Issues and Research Perspectives in Forensic Toxicology)
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Open AccessSystematic Review
Nephrotoxicity of New Antibiotics: A Systematic Review
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Panagiotis Stathopoulos, Laura T. Romanos, Charalampos Loutradis and Matthew E. Falagas
Toxics 2025, 13(7), 606; https://doi.org/10.3390/toxics13070606 (registering DOI) - 19 Jul 2025
Abstract
Drug-induced nephrotoxicity is a common and serious problem in clinical practice. We conducted a systematic review of studies reporting nephrotoxicity events associated with antibiotics approved since 2018. The agents assessed included aztreonam/avibactam, cefepime/enmetazobactam, cefiderocol, ceftobiprole, contezolid, gepotidacin, imipenem/cilastatin/relebactam, lascufloxacin, lefamulin, levonadifloxacin, plazomicin, and
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Drug-induced nephrotoxicity is a common and serious problem in clinical practice. We conducted a systematic review of studies reporting nephrotoxicity events associated with antibiotics approved since 2018. The agents assessed included aztreonam/avibactam, cefepime/enmetazobactam, cefiderocol, ceftobiprole, contezolid, gepotidacin, imipenem/cilastatin/relebactam, lascufloxacin, lefamulin, levonadifloxacin, plazomicin, and sulbactam/durlobactam. Literature searches were conducted in PubMed, Scopus, Web of Science, and major pharmacovigilance databases (Vigibase, FAERS, EudraVigilance, EMA, FDA, NMPA, PMDA, and CDSCO) in May 2025, along with reference citation tracking. Studies were included if they reported safety or adverse event data. The risk of bias was assessed using validated tools in accordance with the study design. Out of 2105 potentially relevant records, 74 studies met inclusion criteria, comprising 52 clinical trials, 17 observational studies, 1 registry-based study, 3 case series, and 1 case report. Nephrotoxicity was rarely reported for any of the newly approved antibiotics. No renal adverse events were found in the available studies for aztreonam/avibactam, levonadifloxacin, and contezolid. Most studies were of moderate to high quality; two were classified as low quality. However, nephrotoxicity was inconsistently assessed, with variable definitions and methodologies used. Although current data suggest a low frequency of nephrotoxicity, limitations in study design and reporting preclude firm conclusions. There is a need for post-marketing studies to better characterize renal safety. Clinicians should remain vigilant and continue to monitor for and report renal-related adverse events.
Full article
(This article belongs to the Special Issue Nephrotoxicity Induced by Drugs and Chemicals in the Environment)
Open AccessArticle
Impact of Polystyrene Microplastics on Human Sperm Functionality: An In Vitro Study of Cytotoxicity, Genotoxicity and Fertility-Related Genes Expression
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Filomena Mottola, Maria Carannante, Ilaria Palmieri, Lorenzo Ibello, Luigi Montano, Mariaceleste Pezzullo, Nicola Mosca, Nicoletta Potenza and Lucia Rocco
Toxics 2025, 13(7), 605; https://doi.org/10.3390/toxics13070605 (registering DOI) - 19 Jul 2025
Abstract
Polystyrene microplastics (PS-MPs) released in the environment reportedly affect the reproduction of various organisms, induced oxidative stress and apoptosis, resulting in altered sperm parameters. In this in vitro study, we tested the cytotoxicity and genotoxicity of PS-MPs by exposing human semen samples to
[...] Read more.
Polystyrene microplastics (PS-MPs) released in the environment reportedly affect the reproduction of various organisms, induced oxidative stress and apoptosis, resulting in altered sperm parameters. In this in vitro study, we tested the cytotoxicity and genotoxicity of PS-MPs by exposing human semen samples to PS-MPs levels (105 and 210 μg/mL) for 30–60–90 min. Semen parameters, genome stability, sperm DNA fragmentation (SDF) and reactive oxygen species (ROS) production were analyzed before and after exposure. Moreover, we also evaluated the expression level of spermatozoa-specific expressed genes essential for the fusion with oocyte (DCST1, DCST2, IZUMO1, SPACA6, SOF1, and TMEM95). After PS-MP exposure, semen concentration and morphology did not differ, while sperm vitality and motility decreased in a time-dependent manner. In addition, sperm agglutination was observed in the groups exposed to both PS-MPs concentrations tested. A time- and concentration-dependent reduction in genomic stability, as well as increased SDF and ROS production, was also observed. Moreover, all investigated transcripts were down-regulated after PS-MP exposure. Our results confirm the oxidative stress-mediated genotoxicity and cytotoxicity of PS-MPs on human spermatozoa. The sperm agglutination observed after treatment could be due to the aggregation of PS-MPs already adhered to the sperm membranes, hindering sperm movement and fertilizing capability. Interestingly, the downregulation of genes required for sperm–oocyte fusion, resulting from data on the in vitro experimental system, suggests that PS-MP exposure may have implications for sperm functionality. While these findings highlight potential mechanisms of sperm dysfunction, further investigations using in vivo models are needed to determine their broader biological implications. Possible environmental and working exposure to pollutants should be considered during the counselling for male infertility.
Full article
(This article belongs to the Section Reproductive and Developmental Toxicity)
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Open AccessArticle
Evaluating Copper-Induced Oxidative Stress in Germinating Wheat Seeds Using Laser Photoacoustic Spectroscopy and EPR Techniques
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Mioara Petrus, Cristina Popa, Ana-Maria Bratu, Alexandra Camelia Joita and Vasile Bercu
Toxics 2025, 13(7), 604; https://doi.org/10.3390/toxics13070604 - 18 Jul 2025
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Copper is an essential micronutrient for plants, but excessive levels can induce toxicity and impair physiological functions. This study evaluates the toxic effects of copper sulfate (CuSO4) on the germination of common wheat (Triticum aestivum), with emphasis on the
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Copper is an essential micronutrient for plants, but excessive levels can induce toxicity and impair physiological functions. This study evaluates the toxic effects of copper sulfate (CuSO4) on the germination of common wheat (Triticum aestivum), with emphasis on the gas emission dynamics and oxidative stress biomarkers. Seeds were germinated in agar and exposed to CuSO4 at concentrations of 1 µM, 100 µM, 1 mM, and 10 mM; distilled water served as the control. Ethylene and ammonia emissions were quantified using CO2 laser photoacoustic spectroscopy, while electron paramagnetic resonance (EPR) spectroscopy was employed to detect free radicals and Cu2+ complexes. Exposure to Cu concentrations ≥ 1 mM significantly inhibited germination and biomass accumulation. Enhanced ethylene and ammonia emissions, particularly at 10 mM, indicated stress-related metabolic responses. The EPR spectra confirmed the presence of semiquinone radicals and Cu2+ complexes under higher Cu levels. These results demonstrate that photoacoustic and EPR techniques are effective tools for the early detection of metal-induced phytotoxicity and offer a non-invasive approach to environmental toxicity screening and plant stress assessment.
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Open AccessArticle
Environmental Risk and Management of Iron Tailings in Road Subgrade
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Xiaowei Xu, Dapeng Zhang, Jie Cao, Chaoyue Wu, Yi Wang, Jing Hua, Zehua Zhao, Jun Zhang and Qi Yu
Toxics 2025, 13(7), 603; https://doi.org/10.3390/toxics13070603 - 17 Jul 2025
Abstract
The utilization of iron tailings in road construction poses significant environmental risks due to the complex release mechanisms of pollutants and varying regional conditions. This study integrates an exponential decay model with an instantaneous pollutant transport model, employing Monte Carlo simulations to assess
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The utilization of iron tailings in road construction poses significant environmental risks due to the complex release mechanisms of pollutants and varying regional conditions. This study integrates an exponential decay model with an instantaneous pollutant transport model, employing Monte Carlo simulations to assess risks and regional characteristics. Results show high Potential Hazard Indices (PHIs) for arsenic, manganese, barium, nickel, and lead, with PHI values between 4.2 and 22.7. Simulations indicate that manganese and nickel concentrations may exceed groundwater standards, particularly in humid areas. The study recommends controlling the iron tailings mixing ratio based on climate, suggesting limits of 35% in humid, 60% in semi-humid, and more lenient ratios in arid and semi-arid regions. It also underscores the need for improved risk assessment methodologies and region-specific management strategies at the national level.
Full article
(This article belongs to the Special Issue Soil Heavy Metal Pollution and Human Health)
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Open AccessArticle
Thermoset Polyester Resin Microplastics: Effects on Enzymatic Biomarkers and Toxicological Endpoint Responses of Eisenia fetida Earthworms
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David Amaya-Vías, Gemma Albendín, Vanessa Aranda-Quirós, Rocío Rodríguez-Barroso, Dolores Coello and Juana María Arellano
Toxics 2025, 13(7), 602; https://doi.org/10.3390/toxics13070602 - 17 Jul 2025
Abstract
Thermosets are plastic composite materials widely used in many industrial sectors of modern society with an increasing presence in the environment. The adverse effects of this material on environmental compartments and biota of thermosets are still unknown. In this work, we studied the
[...] Read more.
Thermosets are plastic composite materials widely used in many industrial sectors of modern society with an increasing presence in the environment. The adverse effects of this material on environmental compartments and biota of thermosets are still unknown. In this work, we studied the potential effects of two thermoset polyester resin-derived microplastics (R930A-SP and R930A-DVE1) on the survival, behavior, morphological changes and subcellular damage of earthworms Eisenia fetida. The proposed experimental conditions simulated environmentally relevant concentrations, taking as a reference other related microplastics present in the environment. Thus, E. fetida specimens were exposed to five concentrations (100, 500, 1000, 1500 and 2000 mg resin per kg soil) of these two resins for 14 days. At concentrations and exposure times studied, no significant effects on growth, measured as weight loss, or on the enzyme biomarkers (cholinesterase, carboxylesterase and glutathione S-transferase) were observed. Similarly, no behavioral changes were detected in earthworms, and the survival rate was 100%. Likewise, no differences were observed between the different formulations of the polyester resins studied. However, this study could serve as a starting point for further studies with higher concentrations and/or exposure times, as well as in combination with other pollutants.
Full article
(This article belongs to the Special Issue Ecotoxicological Effects of Microplastics on the Soil Environment)
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Open AccessArticle
Forty Years After Chernobyl: Radiocaesium in Wild Edible Mushrooms from North-Eastern Poland and Its Relevance for Dietary Exposure and Food Safety
by
Iwona Mirończuk-Chodakowska, Jacek Kapała, Karolina Kujawowicz, Monika Sejbuk and Anna Maria Witkowska
Toxics 2025, 13(7), 601; https://doi.org/10.3390/toxics13070601 - 17 Jul 2025
Abstract
Wild-growing edible mushrooms are known to bioaccumulate radionuclides from their environment, particularly the natural isotope potassium-40 (40K) and anthropogenic cesium-137 (137Cs). However, region-specific data for commercially relevant species in north-eastern Poland remain limited, despite the cultural and economic importance
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Wild-growing edible mushrooms are known to bioaccumulate radionuclides from their environment, particularly the natural isotope potassium-40 (40K) and anthropogenic cesium-137 (137Cs). However, region-specific data for commercially relevant species in north-eastern Poland remain limited, despite the cultural and economic importance of mushroom foraging and export. This study aimed to assess the radiological safety of wild mushrooms intended for human consumption, with particular attention to regulatory compliance and potential exposure levels. In this study, 230 mushroom samples representing 19 wild edible species were analyzed using gamma spectrometry, alongside composite soil samples collected from corresponding foraging sites. The activity concentration of 137Cs in mushrooms ranged from 0.94 to 159.0 Bq/kg fresh mass (f.m.), and that of 40K from 64.4 to 150.2 Bq/kg f.m. None of the samples exceeded the regulatory limit of 1250 Bq/kg f.m. for 137Cs. The highest estimated annual effective dose was 2.32 µSv from 137Cs and 0.93 µSv from 40K, with no exceedance of regulatory limits observed in any sample. A strong positive correlation was observed between 137Cs activity in soil and mushroom dry mass (Spearman’s Rho = 0.81, p = 0.042), supporting predictable transfer patterns. Additionally, the implications of mushroom drying were assessed considering Council Regulation (Euratom) 2016/52, which mandates radionuclide levels in dried products be evaluated based on their reconstituted form. After such adjustment, even the most contaminated dried samples were found to comply with food safety limits. These findings confirm the radiological safety of wild mushrooms from north-eastern Poland and contribute novel data for a region with limited prior monitoring, in the context of current food safety regulations.
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(This article belongs to the Section Agrochemicals and Food Toxicology)
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Open AccessArticle
Immunotoxicity Studies on the Insecticide 2-((1-(4-Phenoxyphenoxy)propan-2-yl)oxy)pyridine (MPEP) in Hsd:Harlan Sprague Dawley SD® Rats
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Victor J. Johnson, Stefanie C. M. Burleson, Michael I. Luster, Gary R. Burleson, Barry McIntyre, Veronica G. Robinson, Reshan A. Fernando, James Blake, Donna Browning, Stephen Cooper, Shawn Harris and Dori R. Germolec
Toxics 2025, 13(7), 600; https://doi.org/10.3390/toxics13070600 - 17 Jul 2025
Abstract
The broad-spectrum insect growth regulator (IGR) and insecticide 2-((1-(4-Phenoxyphenoxy)propan-2-yl)oxy)pyridine (MPEP; also known as pyriproxyfen) is increasingly being used to address public health programs for vector control, initiated by the spread of Zika virus in 2015–2016. While considered relatively safe for humans under normal
[...] Read more.
The broad-spectrum insect growth regulator (IGR) and insecticide 2-((1-(4-Phenoxyphenoxy)propan-2-yl)oxy)pyridine (MPEP; also known as pyriproxyfen) is increasingly being used to address public health programs for vector control, initiated by the spread of Zika virus in 2015–2016. While considered relatively safe for humans under normal conditions, limited toxicology data are available. Current studies were undertaken to address the data gap regarding potential immunotoxicity of MPEP, with particular emphasis on host resistance to viral infection. Hsd:Harlan Sprague Dawley SD® rats were treated for 28 days by oral gavage with doses of 0, 62.5, 125, 250 or 500 mg/kg/day of MPEP in corn oil. There was a dose-dependent increase in liver weights which is consistent with the liver playing a dominant role in MPEP metabolism. However, no histological correlates were observed. Following treatment, rats were subjected to a battery of immune tests as well as an established rat model of influenza virus infection to provide a comprehensive assessment of immune function and host resistance. While several of the immune tests showed minor exposure-related changes, evidenced by negative dose–response trends, most did not show significant differences in any of the MPEP treatment groups relative to vehicle control. Most notable was a negative trend in pulmonary mononuclear cell phagocytosis with increases in dose of MPEP. There was also a positive trend in early humoral immune response (5 days after immunization) to keyhole limpet hemocyanin (KLH) as evidenced by increased serum anti-KLH IgM antibodies which was followed later (14 days following immunization) by decreasing trends in anti-KLH IgM and IgG antibody levels. However, MPEP treatment had no effect on the ability of rats to clear the influenza virus nor the T-dependent IgM and IgG antibody response to the virus. The lack of effects of MPEP on host resistance to influenza suggests the immune effects were minimal and unlikely to present a hazard with respect to susceptibility to respiratory viral infection.
Full article
(This article belongs to the Special Issue Environmental Contaminants and Human Health—2nd Edition)
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Open AccessArticle
Investigation into the Enhancement Effects of Combined Bioremediation of Petroleum-Contaminated Soil Utilizing Immobilized Microbial Consortium and Sudan Grass
by
Tie-Jun Wang, Zi-Yue Ding, Zi-Wei Hua, Zi-Wang Yuan, Qiu-Hong Niu and Hao Zhang
Toxics 2025, 13(7), 599; https://doi.org/10.3390/toxics13070599 - 16 Jul 2025
Abstract
Petroleum-contaminated soil is an increasingly severe environmental issue. The integration of phytoremediation and microbial remediation can effectively mitigate their individual limitations and enhance remediation efficiency. In this study, four newly isolated bacterial strains (including Cytobacillus and Rhodococcus) that exhibited preferential degradation of
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Petroleum-contaminated soil is an increasingly severe environmental issue. The integration of phytoremediation and microbial remediation can effectively mitigate their individual limitations and enhance remediation efficiency. In this study, four newly isolated bacterial strains (including Cytobacillus and Rhodococcus) that exhibited preferential degradation of distinct petroleum components were combined with the rhamnolipid-producing strain Pseudomonas aeruginosa SL-1. The immobilization of this petroleum-degrading microbial consortium was performed by biochar adsorption and sodium alginate embedding, subsequently optimized using response surface methodology (0.75 g·L−1 of biochar, 40 g·L−1 of sodium alginate, and 40 g·L−1 of calcium chloride). The results showed that the highest petroleum degradation rate (97.1%) of immobilized bacterial consortium was achieved at 72 h at a petroleum concentration of 5.0 g·L−1. When combined with Sudan grass for soil bioremediation, the degradation rate reached 72.8% after 120 d for soil containing 5.0 g·kg−1 of petroleum, higher than the results for the treatments with only immobilized bacterial consortium (53.0%) or Sudan grass (49.2%). Furthermore, significant improvements were observed for soil pH; nitrogen, phosphorus, and potassium contents; and urease, dehydrogenase, and catalase activities. Composite treatment also significantly increased the diversity and richness of the soil bacterial community and regulated its structure, function, and network composition. This study offers theoretical insights and potential practical applications for the enhanced bioremediation of petroleum-contaminated soils.
Full article
(This article belongs to the Special Issue Multi-Media Environmental Pollution and Health Risks: Tracing, Effects, and Collaborative Governance)
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Open AccessArticle
Interactive Effects of Ambient Ozone and Meteorological Factors on Cerebral Infarction: A Five-Year Time-Series Study
by
Yanzhe Chen, Songtai Yang, Hanya Que, Jiamin Liu, Zhe Wang, Na Wang, Yunkun Qin, Meng Li and Fang Zhou
Toxics 2025, 13(7), 598; https://doi.org/10.3390/toxics13070598 (registering DOI) - 16 Jul 2025
Abstract
Objective: Our objective was to investigate the short-term effects of ambient ozone (O3) meteorological factors and their interactions on hospitalizations for cerebral infarction in Zhengzhou, China. Methods: Daily data on air pollutants, meteorological factors, and hospitalization of cerebral infarction patients
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Objective: Our objective was to investigate the short-term effects of ambient ozone (O3) meteorological factors and their interactions on hospitalizations for cerebral infarction in Zhengzhou, China. Methods: Daily data on air pollutants, meteorological factors, and hospitalization of cerebral infarction patients were collected from 1 January 2019 to 31 December 2023 in Zhengzhou, China. A generalized additive model was constructed to evaluate the association between ambient O3 levels and hospitalization for cerebral infarction. A distributed lag non-linear model was applied to capture lagged and non-linear exposure effects. We further examined the modifying roles of temperature, humidity, wind speed, and atmospheric pressure, and conducted stratified analyses by sex, age, and season. Results: O3 exposure was significantly associated with increased cerebral infarction risk, particularly during the warm season. A bimodal temperature-lag pattern was observed, as follows: moderate temperatures (10–20 °C) were associated with immediate effects, while cold (<10 °C) and hot (>30 °C) temperatures were linked to delayed risks. The association of O3 and hospitalizations for cerebral infarction appeared stronger under high humidity, low wind speed, and low atmospheric pressure. Conclusions: Short-term O3 exposure and adverse meteorological conditions are jointly associated with an elevated risk of cerebral infarction. Integrated air quality and weather-based warning systems are essential for targeted stroke prevention.
Full article
(This article belongs to the Special Issue Ozone Pollution and Adverse Health Impacts)
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Open AccessArticle
Health Risks from Microplastics in Intravenous Infusions: Evidence from Italy, Spain, and Ecuador
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Claudio Casella, Umberto Cornelli, Giuseppe Zanoni, Pablo Moncayo and Luis Ramos-Guerrero
Toxics 2025, 13(7), 597; https://doi.org/10.3390/toxics13070597 - 16 Jul 2025
Abstract
The rising incidence of microplastics (MPs) is a possible health risk to humans. The present study aims to analyze the presence of MPs in intravenous (IV) infusions and compare MP concentrations from multiple brands. The IV solutions of 29 medical devices (IV-MDs) from
[...] Read more.
The rising incidence of microplastics (MPs) is a possible health risk to humans. The present study aims to analyze the presence of MPs in intravenous (IV) infusions and compare MP concentrations from multiple brands. The IV solutions of 29 medical devices (IV-MDs) from seven brands commercialized in Ecuador, Spain, and Italy have been selected under specific consideration to carry out the study. The detection of MPs has been quite obvious in almost all of the samples from brands in the mentioned countries. MP concentrations ranged from 9 to 20 MPs/L in glass containers to 166–299 MPs/L in plastic bags, with the majority of fragments (63%) on fibres (37%) and more than 60% of particles less than 100 µm. Nine different types of MPs were identified in this study. High clinical risk was indicated by markings with >200 MPs/L. Nevertheless, the medium polymeric danger index (PHI) was 1.7. According to these outcomes, IV infusion is a direct exposure to MPs that may have harmful medical repercussions. It is imperative that MPs’ limitations be included in pharmacopoeic monographs and in vivo toxicological and epidemiological studies. The present study aims to analyze the presence of MPs in IV-MDs and compare MP concentrations from multiple IV-MD brands.
Full article
(This article belongs to the Topic Plastic Contamination (Plastamination): An Environmental and Public Health-Related Concern)
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Open AccessFeature PaperReview
The Aryl Hydrocarbon Receptor in Neurotoxicity: An Intermediator Between Dioxins and Neurons in the Brain
by
Eiki Kimura
Toxics 2025, 13(7), 596; https://doi.org/10.3390/toxics13070596 - 16 Jul 2025
Abstract
Industrial development has increased environmental dioxin concentrations, sparking concern about human health impacts. Examining dioxin neurotoxicity has highlighted associations with cognitive impairment and behavioral abnormality. Dioxins are ligands of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor; it is speculated that dioxin-induced
[...] Read more.
Industrial development has increased environmental dioxin concentrations, sparking concern about human health impacts. Examining dioxin neurotoxicity has highlighted associations with cognitive impairment and behavioral abnormality. Dioxins are ligands of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor; it is speculated that dioxin-induced AHR activation is pivotal for toxic effects. Accurate AHR-expressing cell identification is therefore indispensable for understanding the molecular and cellular mechanisms of dioxin toxicity. Herein, current knowledge regarding AHR expression in the mammalian brain is summarized, and dioxin neurotoxicity mechanisms are discussed. Histological studies show AHR-expressing neurons in multiple brain regions, including the hippocampus and cerebral cortex. Dopaminergic and noradrenergic neurons exhibit AHR expression, suggesting possible roles in the monoaminergic system. AHR overactivation evokes dendritic arborization atrophy, whereas its deficiency increases complexity, implying that AHR-mediated signaling is crucial for neuronal growth and maturation. AHR is also involved in neurogenesis and neuronal precursor migration. Collectively, these findings support the notion that dioxin-induced AHR overactivation in individual neurons disrupts neural circuit structure, ultimately leading to impaired brain function. However, as AHR downstream signaling is intertwined with various molecules and pathways, the precise mechanisms remain unclear. Further studies on the expression, signaling, and roles of AHR are needed to clarify dioxin neurotoxicity.
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(This article belongs to the Section Human Toxicology and Epidemiology)
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Open AccessArticle
Accumulation Patterns and Health Risk Assessment of Trace Elements in Intermuscular Bone-Free Crucian Carp
by
Shizhan Tang, Na Li, Zhipeng Sun, Ting Yan, Tingting Zhang, Huan Xu, Zhongxiang Chen, Dongli Qin and Youyi Kuang
Toxics 2025, 13(7), 595; https://doi.org/10.3390/toxics13070595 - 16 Jul 2025
Abstract
This study investigated the accumulation characteristics and associated health risks of 11 trace elements (Al, Rb, Cr, Ni, Mo, Sr, Pb, Ba, Ag, As, and Ga) in four crucian carp varieties: gene-edited intermuscular bone-free crucian carp (Carassius auratus, WUCI) and its sibling
[...] Read more.
This study investigated the accumulation characteristics and associated health risks of 11 trace elements (Al, Rb, Cr, Ni, Mo, Sr, Pb, Ba, Ag, As, and Ga) in four crucian carp varieties: gene-edited intermuscular bone-free crucian carp (Carassius auratus, WUCI) and its sibling wild-type (Carassius auratus, WT), Fangzheng silver crucian carp (Carassius gibelio var Fangzheng, FZYJ), and Songpu silver crucian carp (Carassius gibelio var Songpu, SPYJ). Results showed that Al and Rb were the most abundant elements across all groups. WUCI exhibited distinct accumulation patterns, including significantly higher hepatic Mo concentrations (0.265 ± 0.032 mg/kg) and muscle/liver Rb levels (muscle: 8.74 ± 1.21 mg/kg; liver: 12.56 ± 2.05 mg/kg) compared to other varieties (p < 0.05), which supports the hypothesis of genotype-specific differences in heavy metal accumulation. Correlation analysis revealed that WUCI exhibited similar elemental interactions with WT and SPYJ (e.g., Al-Ni positive correlation, |rs| ≥ 0.8), while SPYJ displayed distinct patterns with fifteen negative correlations compared to three to five in others varieties, suggesting a potential alteration in elemental homeostasis. Pollution index (Pi) assessments indicated mild contamination for Pb in SPYJ liver (Pi = 0.265) and Cr/As in WUCI muscle (Pi = 0.247/0.218). Despite these values, all hazard indices remained below the established safety thresholds (THQ < 0.1, HI < 0.25, TCR < 10−6), reinforcing the overall safety of the tested fish. Notably, muscle As levels (0.86 ± 0.15 mg/kg) exceeded hepatic concentrations (0.52 ± 0.09 mg/kg), potentially due to differential detoxification mechanisms. These findings demonstrate the food safety of all tested varieties, while highlighting genotype-specific metabolic adaptations, providing critical data for evaluating gene edited aquatic products.
Full article
(This article belongs to the Special Issue Effects of Toxic Contaminants on Fish Behaviours)
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Open AccessArticle
Liraglutide Attenuates Atorvastatin-Induced Hepatotoxicity by Restoring GLP-1R Expression and Activating Nrf2 and Autophagy Pathways in Wistar Rats
by
Engy A. Elsiad, Hayat A. Abd El Aal, Hesham A. Salem, Mohammed F. El-Yamany and Mostafa A. Rabie
Toxics 2025, 13(7), 594; https://doi.org/10.3390/toxics13070594 - 16 Jul 2025
Abstract
HMG-CoA reductase inhibitors, statins, are extensively used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic disorders. However, one of the common side effects of statin therapy is a mild elevation in liver aminotransferases, observed in less than 3% of patients. Atorvastatin and
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HMG-CoA reductase inhibitors, statins, are extensively used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic disorders. However, one of the common side effects of statin therapy is a mild elevation in liver aminotransferases, observed in less than 3% of patients. Atorvastatin and simvastatin, in particular, are most frequently associated with statin-induced liver injury, leading to treatment discontinuation. Recent research has highlighted the antioxidant and anti-inflammatory properties of glucagon-like peptide-1 receptor (GLP-1R) activation in protecting against liver injury. Nonetheless, the potential protective effects of liraglutide (LIRA), a GLP-1R agonist, against atorvastatin (ATO)-induced liver dysfunction have not been fully elucidated. In this context, the present study aimed to investigate the protective role of LIRA in mitigating ATO-induced liver injury in rats, offering new insights into managing statin-associated hepatotoxicity. Indeed, LIRA treatment improved liver function enzymes and attenuated histopathological alterations. LIRA treatment enhanced antioxidant defenses by increasing Nrf2 content and superoxide dismutase (SOD) activity, while reducing NADPH oxidase. Additionally, LIRA suppressed inflammation by downregulating the HMGB1/TLR-4/RAGE axis and inhibiting the protein expression of pY323-MAPK p38 and pS635-NFκB p65 content resulting in decreased proinflammatory cytokines (TNF-α and IL-1β). Furthermore, LIRA upregulated GLP-1R gene expression and promoted autophagic influx via the activation of the pS473-Akt/pS486-AMPK/pS758-ULK1/Beclin-1 signaling cascade, along with inhibiting apoptosis by reducing caspase-3 content. In conclusion, LIRA attenuated ATO-induced oxidative stress and inflammation via activation of the Nrf-2/SOD cascade and inhibition of the HMGB1/TLR-4/RAGE /MAPK p38/NFκB p65 axis. In parallel, LIRA stimulated autophagy via the AMPK/ULK1/Beclin-1 axis and suppressed apoptosis, thus restoring the balance between autophagy and apoptosis.
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(This article belongs to the Section Drugs Toxicity)
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Cadmium as the Critical Limiting Factor in the Co-Disposal of Municipal Solid Waste Incineration Fly Ash in Cement Kilns: Implications for Three-Stage Water Washing Efficiency and Safe Dosage Control
by
Zhonggen Li, Qingfeng Wang, Li Tang, Liangliang Yang and Guangyi Sun
Toxics 2025, 13(7), 593; https://doi.org/10.3390/toxics13070593 - 15 Jul 2025
Abstract
The co-disposal of municipal solid waste incineration fly ash (MSWI-FA) in cement kilns is an effective method for managing incineration by-products in China. However, the presence of heavy metals in MSWI-FA raises environmental concerns. This study analyzed the Cu, Zn, Cd, Pb, Cr,
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The co-disposal of municipal solid waste incineration fly ash (MSWI-FA) in cement kilns is an effective method for managing incineration by-products in China. However, the presence of heavy metals in MSWI-FA raises environmental concerns. This study analyzed the Cu, Zn, Cd, Pb, Cr, and Ni concentrations in MSWI-FA from 11 representative facilities across China and assessed the efficacy of a three-stage water washing process for Cl and heavy metal removal. The results revealed significant regional variations in heavy metal content that were strongly correlated with surface soil levels, with Zn, Pb, and Cu exhibiting the highest concentrations. Elemental correlations, such as Cu-Pb and Zn-Cd synergies and Cd-Ni antagonism, suggest common waste sources and temperature-dependent volatilization during incineration. The washing process (solid–liquid ratio = 1:10) achieved 97.1 ± 2.0% Cl removal, reducing residual Cl to 0.45 ± 0.32%, but demonstrated limited heavy metal elimination (10.28–19.38% efficiency), resulting in elevated concentrations (32.5–60.8% increase) due to 43.4 ± 9.2% mass loss. Notably, the washing effluents exceeded municipal wastewater discharge limits by up to 52-fold for Pb and 38-fold for Cd, underscoring the need for advanced effluent treatment. To mitigate environmental risks, the addition of washed MSWI-FA in cement kilns should be restricted to ≤0.5%, with Cd content prioritized in pre-disposal assessments. This study provides actionable insights for optimizing MSWI-FA co-processing while ensuring compliance with ecological safety standards.
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(This article belongs to the Special Issue Distribution and Behavior of Trace Metals in the Environment)
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Acute Dermatotoxicity of Green-Synthesized Silver Nanoparticles (AgNPs) in Zebrafish Epidermis
by
Grace Emily Okuthe and Busiswa Siguba
Toxics 2025, 13(7), 592; https://doi.org/10.3390/toxics13070592 - 15 Jul 2025
Abstract
Silver nanoparticles (AgNPs), lauded for their unique antibacterial and physicochemical attributes, are proliferating across industrial sectors, raising concerns about their environmental fate, in aquatic systems. While “green” synthesis offers a sustainable production route with reduced chemical byproducts, the safety of these AgNPs for
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Silver nanoparticles (AgNPs), lauded for their unique antibacterial and physicochemical attributes, are proliferating across industrial sectors, raising concerns about their environmental fate, in aquatic systems. While “green” synthesis offers a sustainable production route with reduced chemical byproducts, the safety of these AgNPs for aquatic fauna remains uncertain due to nanoparticle-specific effects. Conversely, mast cells play crucial roles in fish immunity, orchestrating innate and adaptive immune responses by releasing diverse mediators and recognizing danger signals. Goblet cells are vital for mucosal immunity and engaging in immune surveillance, regulation, and microbiota interactions. The interplay between these two cell types is critical for maintaining mucosal homeostasis, is central to defending against fish diseases and is highly responsive to environmental cues. This study investigates the acute dermatotoxicity of environmentally relevant AgNP concentrations (0, 0.031, 0.250, and 5.000 μg/L) on zebrafish epidermis. A 96 h assay revealed a biphasic response: initial mucin hypersecretion at lower AgNP levels, suggesting an early stress response, followed by a concentration-dependent collapse of mucosal integrity at higher exposures, with mucus degradation and alarm cell depletion. A rapid and generalized increase in epidermal mucus production was observed across all AgNP exposure groups within two hours of exposure. Further mechanistic insights into AgNP-induced toxicity were revealed by concentration-dependent alterations in goblet cell dynamics. Lower AgNP concentrations initially led to an increase in both goblet cell number and size. However, at the highest concentration, this trend reversed, with a significant decrease in goblet cell numbers and size evident between 48 and 96 h post-exposure. The simultaneous presence of neutral and acidic mucins indicates a dynamic epidermal response suggesting a primary physical barrier function, with acidic mucins specifically upregulated early on to enhance mucus viscosity, trap AgNPs, and inhibit pathogen invasion, a clear defense mechanism. The subsequent reduction in mucin-producing cells at higher concentrations signifies a critical breakdown of this protective strategy, leaving the epidermis highly vulnerable to damage and secondary infections. These findings highlight the vulnerability of fish epidermal defenses to AgNP contamination, which can potentially compromise osmoregulation and increase susceptibility to threats. Further mechanistic research is crucial to understand AgNP-induced epithelial damage to guide sustainable nanotechnology.
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(This article belongs to the Section Ecotoxicology)
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Open AccessCorrection
Correction: Carfora et al. Helium Suicide, a Rapid and Painless Asphyxia: Toxicological Findings. Toxics 2022, 10, 424
by
Anna Carfora, Raffaella Petrella, Giusy Ambrosio, Pasquale Mascolo, Bruno Liguori, Christian Juhnke, Carlo Pietro Campobasso and Thomas Keller
Toxics 2025, 13(7), 591; https://doi.org/10.3390/toxics13070591 - 15 Jul 2025
Abstract
Text Correction [...]
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New QSAR Models to Predict Human Transthyretin Disruption by Per- and Polyfluoroalkyl Substances (PFAS): Development and Application
by
Marco Evangelista, Nicola Chirico and Ester Papa
Toxics 2025, 13(7), 590; https://doi.org/10.3390/toxics13070590 - 14 Jul 2025
Abstract
Per- and polyfluoroalkyl substances (PFAS) are of concern because of their potential thyroid hormone system disruption by binding to human transthyretin (hTTR). However, the amount of experimental data is scarce. In this work, new classification and regression QSARs were developed to predict the
[...] Read more.
Per- and polyfluoroalkyl substances (PFAS) are of concern because of their potential thyroid hormone system disruption by binding to human transthyretin (hTTR). However, the amount of experimental data is scarce. In this work, new classification and regression QSARs were developed to predict the hTTR disruption based on experimental data measured for 134 PFAS. Bootstrapping, randomization procedures, and external validation were used to check for overfitting, to avoid random correlations, and to evaluate the predictivity of the QSARs, respectively. The best QSARs were characterized by good performances (e.g., training and test accuracies in classification of 0.89 and 0.85, respectively; R2, Q2loo, and Q2F3 in regression of 0.81, 0.77, and 0.82, respectively) and significantly broader domains compared to the few existing similar models. The application of QSARs application to the OECD List of PFAS allowed for the identification of structural categories of major concern, such as per- and polyfluoroalkyl ether-based, perfluoroalkyl carbonyl, and perfluoroalkane sulfonyl compounds. Forty-nine PFAS showed a stronger binding affinity to hTTR than the natural ligand T4. Uncertainty quantification for each model and prediction further enhanced the reliability assessment of predictions. The implementation of the new QSARs in non-commercial software facilitates their application to support future research efforts and regulatory actions.
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(This article belongs to the Special Issue Computational Toxicology: Exposure and Assessment)
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Developmental Exposures to Three Mammalian Teratogens Produce Dysmorphic Phenotypes in Adult Caenorhabditis elegans
by
Piper Reid Hunt, Martine Ferguson, Nicholas Olejnik, Jeffrey Yourick and Robert L. Sprando
Toxics 2025, 13(7), 589; https://doi.org/10.3390/toxics13070589 - 14 Jul 2025
Abstract
Efficient new methods are needed to support initiatives to reduce, refine, and/or replace toxicity testing in vertebrates. 5-fluorouracil (5FU), hydroxyurea (HU), and ribavirin (RV) are mammalian teratogens. Skeletal, endocrine organ, and cardiac effects are often associated with teratogenesis, and a simple nematode like
[...] Read more.
Efficient new methods are needed to support initiatives to reduce, refine, and/or replace toxicity testing in vertebrates. 5-fluorouracil (5FU), hydroxyurea (HU), and ribavirin (RV) are mammalian teratogens. Skeletal, endocrine organ, and cardiac effects are often associated with teratogenesis, and a simple nematode like C. elegans lacks these systems. However, many genetic pathways required for mammalian morphogenesis have at least some conserved elements in this small, invertebrate model. The C. elegans lifecycle is 3 days. The effects of 5FU, HU, and RV on the C. elegans morphology were evaluated on day 4 post-initiation of the feeding after hatching for continuous and 24 h (early-only) developmental exposures. Continuous exposures to 5FU and HU induced increases in the incidences of abnormal gonadal structures that were significantly reduced in early-only exposure groups. The incidence of prolapse increased with continuous 5FU and HU exposures and was further increased in early-only exposure groups. Intestinal prolapse through the vulval muscle in C. elegans may be related to reported 5FU and HU effects on skeletal muscle and the gastrointestinal tract in mammals. Continuous RV exposures induced a phenotype lacking a uterus and gonad arms, as well as vulval anomalies that were largely, but not completely, reversed with early-only exposures, which is consistent with reported reversible reproductive tract anomalies after an RV exposure in mammals. These findings suggest that C. elegans can be used to detect the hazard risk from chemicals that adversely affect conserved pathways involved in organismal morphogenesis, but to determine the fit-for-purpose use of this model in chemical safety evaluations, further studies using larger and more diverse chemical test panels are needed.
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(This article belongs to the Section Novel Methods in Toxicology Research)
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Evaluation of Fly Ash Composition from Municipal Solid Waste Incinerators: The Role of the Incinerator Type and Flue Gas Deacidification Process
by
Xuetong Qu, Yanan Wang, Feifei Chen, Chuqiao Li, Yunfei He, Jibo Dou, Shuai Zhang, Jiafeng Ding, Hangjun Zhang and Yuchi Zhong
Toxics 2025, 13(7), 588; https://doi.org/10.3390/toxics13070588 - 14 Jul 2025
Abstract
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The resource utilization potential and environmental impact of fly ash from municipal solid waste incinerators (MSWIs) have attracted wide attention. In this study, four MSWIs in Hangzhou, Zhejiang Province were selected to systematically evaluate the effects of different incinerator types and flue gas
[...] Read more.
The resource utilization potential and environmental impact of fly ash from municipal solid waste incinerators (MSWIs) have attracted wide attention. In this study, four MSWIs in Hangzhou, Zhejiang Province were selected to systematically evaluate the effects of different incinerator types and flue gas deacidification processes on fly ash’s oxide and heavy metal components and their temporal changes as well as conduct risk assessment. The results showed that the contents of MgO, Al2O3, SiO2, and Fe2O3 in the grate furnace fly ash were significantly lower than those in the fluidized bed fly ash, but the compressive strength of its fly ash was high. Chemicals added during the flue gas deacidification process such as CaO and NaHCO3 significantly affected the contents of CaO and Na2O. In addition, heavy metals such as Cu, Mn, Cr, and Ni were mainly distributed in the fluidized bed fly ash, while heavy metals such as Pb and Cd were mainly collected in the grate furnace fly ash. The concentrations of various components in the fly ash fluctuated but were not significant under different time dimensions. Risk assessment indicated that heavy metals such as Cd, Pb, and Sb posed a high risk. This study is expected to provide theoretical support for the safe management and resource utilization of fly ash.
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